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Biomedical subjects

A Genazzani

Publications and source records attributed to A Genazzani.

17 recordsLinked to original sources

Calcineurin controls the expression of isoform 4CII of the plasma membrane Ca(2+) pump in neurons.

The expression of the CII splice variant of the plasma membrane Ca(2+) ATPase 4 (PMCA4) was down-regulated in granule neurons when they were cultured under conditions of partial membrane depolarization (25 mM KCl), which are required for long term in vitro survival of the neurons. These conditions, which cause a chronic increase of the resting free Ca(2+) concentration in the neurons, have recently been shown to promote up-regulation of the PMCA2, 3, and 1CII isoforms. Whereas the chronic, i.e. >3 days, Ca(2+) increase was necessary for the up-regulation of the PMCA1CII, 2, and 3, the down-regulation of the PMCA4CII mRNA was already evident 1-2 h after the start of culturing in 25 mM KCl. The immunosuppressant calcineurin inhibitor FK506 inhibited the down-regulation of the PMCA4CII at both the protein and the mRNA level but did not affect the changes of the other PMCA pumps. Direct evidence for the involvement of calcineurin in the down-regulation of the PMCA4CII was obtained by overexpressing a truncated, constitutively active, and Ca(2+)-independent form of calcineurin; under these conditions, depolarization was not required for the down-regulation of the PMCA4CII pump. De novo synthesis of (transcription) factors was required for the down-regulation of the PMCA4CII mRNA. Calcineurin, therefore, controls the neuronal transcription of PMCA4CII, a splice variant of the pump isoforms that is found almost exclusively in brain.

Animals↗

Calcium controls the transcription of its own transporters and channels in developing neurons.

Calcium has now become important as a regulator of gene expression. Cerebellar granule cells developing in culture undergo early apoptosis unless their calcium is permitted to increase, e.g., by depolarizing their plasma membrane. The increase is kept within controlled limits by changing the pattern of transcription of calcium transporters: The IP(3) channel (but not the ryanodine channel) becomes strongly up-regulated after some days in culture in a reaction which is controlled by calcineurin. Two plasma membrane calcium pumps (isoforms PMCA2 and PMCA3) also become strongly up-regulated after some days; one (PMCA1) experiences instead a splicing switch which up-regulates a truncated variant of the isoform. By contrast, one splicing variant of the isoform PMCA4 and one of the Na/Ca exchangers of the plasma membrane (NCX2) become very rapidly down-regulated: Their down-regulation is also controlled by calcineurin. The altered pattern of Ca(2+) transporter expression is likely to reflect development-linked changes in the demands for calcium signaling in different domains of the neuronal cell.

Animals↗

Effects of a yeast-based dietary supplementation on premenstrual syndrome. A double-blind placebo-controlled study.

A dietary approach has proven to be effective in alleviating symptoms of premenstrual syndrome. In our previous studies, magnesium improved premenstrual irritability and mood scoings. In this double-blind, placebo-controlled study, we evaluated the effects of a new dietetic preparation (Sillix Donna, Giuliani) in 40 patients affected by mild to moderate premenstrual syndrome. Premenstrual symptoms were scored in both follicular and luteal phases, at baseline, at 2nd, 4th and 6th month of treatment by using the Menstrual Distress Questionnaire (MDQ). Twenty patients were randomised to receive the active preparation and 20 placebo. MDQ scores at baseline were similar in the two groups. Five patients of the placebo group dropped out because of treatment failure. No side effects were observed. Both treatments reduced symptoms already in the 2nd month, but the active preparation was more effective at all time controls (p < 0.05); at the 6th month it significantly reduced premenstrual MDQ scores to 18% of baseline values, placebo only to 73%. These data demonstrate that Sillix Donna is effective in reducing premenstrual distress.

Adult↗

Menstrually Related Disorders: points of consensus, debate, and disagreement.

It seems that during the past decade we have been witnessing an evolution of a consensus on the phenomenology and time course of various types of MRDs. We are in a stage in which definitions and diagnostic criteria can be developed, but their broad acceptance is still not assured. The etiology and pathophysiology are still fiercely debated, but reasonable and feasible methods for scientific elucidation of the various hypotheses are in place and are followed by solid groups. Despite the uncertainty concerning the etiology of MRDs, reasonably efficient treatment modalities do exist, and most sufferers of MRDs should expect an eventual alleviation of their symptoms if they are treated in a specialized, established, and up-to-date program.

Female↗

Reduced spinal bone density in young women with amenorrhoea.

To assess the influence of diminished oestrogen production on bone density, we studied 23 amenorrhoeic women and 20 controls (age range 16-29 years) divided into four groups: group 1: 6 patients with idopathic hypogonadotrophic hypogonadism with primary amenorrhoea (IHH); group 2: 5 patients with delayed puberty owing to thalassaemia major (TM); group 3: 12 patients with secondary hypothalamic amenorrhoea (HA); group 4: 20 women with normal menses (controls). Secondary sexual characteristics had developed in all except the women with TM. Groups 1 and 2 had never menstruated and group 3 had been amenorrhoeic for 6 months to 3 years. The control group was studied during the follicular phase of the cycle. None of the patients were taking oestrogens at the time of observation. Plasma concentrations were determined for 17 beta-oestradiol (E2), deidroepiandrosterone sulphate (DHEA-S), cortisol (F), prolactin (PRL), thyroid hormones (T3 and T4), and gonadotrophins (LH and FSH). Spinal bone mineral density (BMD g/cm2) was assessed by dual photon absorbiometry. BMD (mean +/- 1SD) was reduced in the patients (group 2: 0.920 +/- 0.95; group 1: 0.980 +/- 0.94; and group 3: 1.037 +/- 0.75) as compared with the controls (1.290 +/- 0.95) (P less than 0.01). In the three groups of patients, plasma E2 levels were lower than 50 pg/ml and were positively correlated with the BMD. As expected, plasma gonadotrophin levels were highly and significantly reduced (P less than 0.01) in the patients, compared with that of the controls. These results suggest that reduced spinal BMD in hypogonadic women may be related to the lack of oestrogenic influence on bone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prevalence of different types of human papillomavirus in cervical infection of north Italian women.

We investigated the prevalences of human papillomavirus (HPV) of type 6, 11, 16, 18, 31, 33, 35 and 42 in 276 cervical tissue samples biopsied from a group of North-Italian women in which a HPV infection of the cervix had been suspected. The specimens were evaluated by conventional histological examination and by HPV typing, using Southern blot hybridization on the extracted DNA. We related different degrees of squamous cervical dysplasia, showing or not viral cytopathic effects, with the HPV types harboured in the lesions. Significant rising of HPV 16 prevalences was observed proceeding from mild to moderate and to severe dysplasias both in presence (r = 0.9623, P less than 0.01) and in absence (r = 0.879, P less than 0.05) of koilocytosis, while an opposite trend was detected for HPV 6 and 11. In our sampling we did not find HPV 35 DNA sequences; in all occasions HPV 31 was associated with mild dysplasias. The absolute prevalences of types 18, 33 and 42 were generally low (from 2 to 3%); they did not show any association with specific histological damage of the cervix or with significant patterns related with the progression of cervical dysplasia.

Condylomata Acuminata↗

Bromocriptine in the Rett syndrome.

Twelve typical cases of the Rett syndrome and one forme fruste were treated with bromocriptine for six months and then had a washout for two months followed by resumption of the bromocriptine treatment. During the first bromocriptine treatment there were improvements in communication and relaxation in some of the girls: a more regular sleep pattern was observed in 4 and a more varied facial expression in 8, and 4 girls began to utter a few words. The bouts of hyperpnea disappeared in 5 and grinding of the teeth in 3. There was also a reduction in stereotypic hand activities in 5 girls and signs of improved motor abilities in 3. The washout caused a general decrease in the positive effects of the previously administered bromocriptine and resumption of the treatment with this drug led to less marked improvement. Metoclopramide was tested in all the girls before the treatment, and it was noted that, while endorphins were hyporesponsive, prolactin was hyperresponsive. This test was repeated two months after the bromocriptine treatment had been performed and, while beta-lipotropin remained unchanged, beta-endorphin showed increased responsiveness.

Adolescent↗

Hormonal mechanism of milk secretion in the newborn.

The mechanism inducing milk secretion in 10 puerperal women and in their children (Witch's milk) was studied by means of sequential hormone measurements starting at delivery and continued during the first postpartum week. Determinations included prolactin (PRL), growth hormone (GH), estradiol 17beta (E217beta), and progesterone (PG). Hormonal levels in the newborns closely paralleled those of the mothers. In both groups, the onset of milk secretion coincided with the disappearance of sex steroids from plasma in the presence of elevated PRL concentrations. Response to TRH (8 microng/kg) revealed adequate PRL reserve, and failure of this peptide to modify basal GH in the neonates was suggestive of appropriate hypothalamic control. The role of estrogens in the induction of pituitary hyperplasia during pregnancy is discussed.

Estradiol↗

Seminal fluid androgen levels in infertile patients.

Seminal fluid concentrations of testosterone (T), dihydrotestosterone (DHT), androstenedione (A), and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) were measured in 34 male patients of infertile couples. Patients were subdivided into oligospermic (less than 20 X 10(6)/mL) and asthenospermic (typical motility less than 20%; total motility less than 40%) groups. Steroids were measured by specific radioimmunoassay after ether extraction and celite column chromatography. 3 alpha-Diol was present in seminal fluid, and its concentration was significantly correlated with DHT (r = .49, P less than .05). In oligospermic patients, seminal levels of T (78 +/- 29 pg/mL, mean +/- SD) and DHT (323 +/- 132 pg/mL) were significantly reduced in comparison with normospermic men (T, 119 +/- 56, P less than .05; DHT, 557 +/- 255, P less than .01), while A and 3 alpha-diol concentrations were similar in the two groups. Seminal T and DHT levels were also reduced in asthenospermic specimens, which showed increased 3 alpha-diol concentrations (75 +/- 44 pg/mL) with respect to normokinetic samples (45 +/- 20, P less than .05). Finally, a positive linear relationship was observed between DHT and both sperm density (P less than .01) and total motility (P less than .01). These data demonstrate the existence of a significant amount of 3 alpha-diol in seminal plasma and suggest DHT as the androgen most closely related to sperm quality.

Adult↗